miRNAs role in cervical cancer pathogenesis and targeted therapy: Signaling pathways interplay

Doghish, Ahmed S.; Mohamed, Azah; Elyan, Salah S.; Elrebehy, Mahmoud A.; Mohamed, Hend H.; Mansour, Reda M.; Elgohary, Ayatallah; Ghanem, Aml; Faraag, Ahmed Hassan Ibrahim; Abdelmaksoud, Nourhan M.; Moustafa, Hebatallah Ahmed Mohamed

doi:10.1016/j.prp.2023.154386

Cited by 33 publications

(10 citation statements)

References 167 publications

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“…It was later found that enoxacin's stimulatory effect on the miRNA pathway promotes apoptosis in several types of cancer cells 15,27,28 . Since miRNAs play important roles in esophageal cancer cells [29][30][31] , we hypothesized that enoxacin might inhibit these cells via enhancing the RNAi pathway. We observed that enoxacin treatment markedly reduced cell survival, ability to proliferation, colony formation, and migration ability of ESCC cells, but had no negative effects on the viability of normal cells as expected, because the drug had previously been approved by several international food and drug administrations to be safe for use in humans as an antibiotic.…”

Section: Discussionmentioning

confidence: 99%

The RNAi enhancer enoxacin inhibits the growth and migration of esophageal squamous cell carcinoma cells

Torabi,

Torkian,

Miri

et al. 2024

Preprint

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Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers worldwide. A decrease in the global expression of microRNAs (miRNAs) is observed in various types of cancer, including esophageal cancer. It has been found that the small molecule enoxacin serves as an RNA interference (RNAi) enhancer, increasing the maturation rate of various cellular miRNAs. Here, we show that enoxacin significantly reduces the growth characteristics of ESCC cell lines. It induces cell cycle arrest and apoptosis in ESCC cells, leading to a clear decrease in ESCC cell number and viability. In addition, enoxacin suppresses the ability of cells to migrate and decreases their capacity to form colonies. Mechanistically, we reveal that enoxacin promotes the maturation of miRNAs through the stimulation of TARBP2 protein, the physical partner of DICER1. Taken together, enoxacin potently blocks the growth, motility, and clonogenicity of ESCC cells, paving the way for further investigation of this small-molecule chemical in animal models of ESCC.

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Section: Discussionmentioning

confidence: 99%

The RNAi enhancer enoxacin inhibits the growth and migration of esophageal squamous cell carcinoma cells

Torabi,

Torkian,

Miri

et al. 2024

Preprint

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“…In addition, the targeting of cells within a tumor by certain drugs may not always be a viable option due to limited difusion capabilities and challenges in regulating the drug release mechanism, which can be attributed to the unpredictable nature of the approach. Hence, there is an urgent need for therapeutics that can actively and passively target malignant cells [86,87].…”

Section: Esophageal Cancermentioning

confidence: 99%

Chitosan and Its Derivative-Based Nanoparticles in Gastrointestinal Cancers: Molecular Mechanisms of Action and Promising Anticancer Strategies

Shokati Eshkiki,

Mansouri,

Karamzadeh

et al. 2024

Journal of Clinical Pharmacy and Therapeutics

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Gastrointestinal cancers account for a significant health concern as the existing treatment modalities, such as surgery, chemotherapy, and radiation therapy, exhibit considerable drawbacks, including a high probability of recurrence, insufficient drug specificity, and severe adverse effects. Hence, novel therapeutic approaches and enhanced tissue-specific targeting are required. Nanomedicine is a field of medicine that uses nanoscale carriers for targeting and administering drugs or diagnostic agents to particular tissues. In the field of nanomedicine, chitosan nanoparticles are well-established delivery technologies used as polymeric carriers. Chitosan is a natural carbohydrate that is biocompatible, biodegradable, polycationic, and mucoadhesive. Chitosan has shown promise in the administration of chemotherapeutic drugs, gene therapy, and immunotherapy for the treatment of gastrointestinal cancers. The limited water solubility of chitosan is one of its major disadvantages as a drug delivery system. Thus, solubility may be increased by chemically treating chitosan. Chitosan derivatives improve the activity, selectivity, biocompatibility, and therapeutic dose reduction of anticancer drugs when used in hydrogel, emulsion, surfactant formulations, and nanoformulation. Chitosan and its derivatives have shown effectiveness in nanoparticle production and exhibit unique surface properties, enabling them to interact selectively with gastrointestinal tumors through both active and passive targeting mechanisms. This review focuses on the molecular signaling pathways of chitosan nanoparticles and their derivatives as potential anticancer agents. The potential of future chitosan applications in gastrointestinal cancers is additionally highlighted.

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“…External beam and internally delivered radiation (brachytherapy) are often used in the radiotherapy of cervical cancer [ 17 , 18 ]. Newer treatments, such as targeted therapy and immunotherapy, have been used in the last decades, including current FDA approval of the combination of pembrolizumab and chemoradiotherapy for the treatment of newly diagnosed, high-risk, locally advanced cervical cancer [ 19 , 20 , 21 , 22 , 23 , 24 ]. However, limitations of these approaches include long treatment regimens, side effects, and high costs that drive persistent disparities and impact patient’s overall quality of life [ 25 , 26 , 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

Investigating the Use of a Liquid Immunogenic Fiducial Eluter Biomaterial in Cervical Cancer Treatment

Moreau,

Keno,

China

et al. 2024

Cancers

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Globally, cervical cancer is the fourth leading cancer among women and is dominant in resource-poor settings in its occurrence and mortality. This study focuses on developing liquid immunogenic fiducial eluter (LIFE) Biomaterial with components that include biodegradable polymers, nanoparticles, and an immunoadjuvant. LIFE Biomaterial is designed to provide image guidance during radiotherapy similar to clinically used liquid fiducials while enhancing therapeutic efficacy for advanced cervical cancer. C57BL6 mice were used to grow subcutaneous tumors on bilateral flanks. The tumor on one flank was then treated using LIFE Biomaterial prepared with the immunoadjuvant anti-CD40, with/without radiotherapy at 6 Gy. Computed tomography (CT) and magnetic resonance (MR) imaging visibility were also evaluated in human cadavers. A pharmacodynamics study was also conducted to assess the safety of LIFE Biomaterial in healthy C57BL6 female mice. Results showed that LIFE Biomaterial could provide both CT and MR imaging contrast over time. Inhibition in tumor growth and prolonged significant survival (* p < 0.05) were consistently observed for groups treated with the combination of radiotherapy and LIFE Biomaterial, highlighting the potential for this strategy. Minimal toxicity was observed for healthy mice treated with LIFE Biomaterial with/without anti-CD40 in comparison to non-treated cohorts. The results demonstrate promise for the further development and clinical translation of this approach to enhance the survival and quality of life of patients with advanced cervical cancer.

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miRNAs role in cervical cancer pathogenesis and targeted therapy: Signaling pathways interplay

Cited by 33 publications

References 167 publications

The RNAi enhancer enoxacin inhibits the growth and migration of esophageal squamous cell carcinoma cells

The RNAi enhancer enoxacin inhibits the growth and migration of esophageal squamous cell carcinoma cells

Chitosan and Its Derivative-Based Nanoparticles in Gastrointestinal Cancers: Molecular Mechanisms of Action and Promising Anticancer Strategies

Investigating the Use of a Liquid Immunogenic Fiducial Eluter Biomaterial in Cervical Cancer Treatment

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